Monitoring of cerebral blood flow autoregulation: physiologic basis, measurement, and clinical implications.

Cerebral blood flow (CBF) autoregulation is the physiologic process whereby blood supply to the brain is kept constant over a range of cerebral perfusion pressures ensuring a constant supply of metabolic substrate. Clinical methods for monitoring CBF autoregulation were first developed for neurocritically ill patients and have been extended to surgical patients. These methods are based on measuring the relationship between cerebral perfusion pressure and surrogates of CBF or cerebral blood volume (CBV) at low frequencies (<0.05 Hz) of autoregulation using time or frequency domain analyses. Initially intracranial pressure monitoring or transcranial Doppler assessment of CBF velocity was utilised relative to changes in cerebral perfusion pressure or mean arterial pressure. A more clinically practical approach utilising filtered signals from near infrared spectroscopy monitors as an estimate of CBF has been validated. In contrast to the traditional teaching that 50 mm Hg is the autoregulation threshold, these investigations have found wide interindividual variability of the lower limit of autoregulation ranging from 40 to 90 mm Hg in adults and 20-55 mm Hg in children. Observational data have linked impaired CBF autoregulation metrics to adverse outcomes in patients with traumatic brain injury, ischaemic stroke, subarachnoid haemorrhage, intracerebral haemorrhage, and in surgical patients. CBF autoregulation monitoring has been described in both cardiac and noncardiac surgery. Data from a single-centre randomised study in adults found that targeting arterial pressure during cardiopulmonary bypass to above the lower limit of autoregulation led to a reduction of postoperative delirium and improved memory 1 month after surgery compared with usual care. Together, the growing body of evidence suggests that monitoring CBF autoregulation provides prognostic information on eventual patient outcomes and offers potential for therapeutic intervention. For surgical patients, personalised blood pressure management based on CBF autoregulation data holds promise as a strategy to improve patient neurocognitive outcomes.

Cerebrovascular responses to a 90° tilt in healthy neonates.

BACKGROUND: Tilts can induce alterations in cerebral hemodynamics in healthy neonates, but prior studies have only examined systemic parameters or used small tilt angles (<90°). The healthy neonatal population, however, are commonly subjected to large tilt angles (≥90°). We sought to characterize the cerebrovascular response to a 90° tilt in healthy term neonates. METHODS: We performed a secondary descriptive analysis on 44 healthy term neonates. We measured cerebral oxygen saturation (rcSO2), oxygen saturation (SpO2), heart rate (HR), breathing rate (BR), and cerebral fractional tissue oxygen extraction (cFTOE) over three consecutive 90° tilts. These parameters were measured for 2-min while neonates were in a supine (0°) position and 2-min while tilted to a sitting (90°) position. We measured oscillometric mean blood pressure (MBP) at the start of each tilt. RESULTS: rcSO2 and BR decreased significantly in the sitting position, whereas cFTOE, SpO2, and MBP increased significantly in the sitting position. We detected a significant position-by-time interaction for all physiological parameters. CONCLUSION: A 90° tilt induces a decline in rcSO2 and an increase in cFTOE in healthy term neonates. Understanding the normal cerebrovascular response to a 90° tilt in healthy neonates will help clinicians to recognize abnormal responses in high-risk infant populations. IMPACT: Healthy term neonates (≤14 days old) had decreased cerebral oxygen saturation (~1.1%) and increased cerebral oxygen extraction (~0.01) following a 90° tilt. We detected a significant position-by-time interaction with all physiological parameters measured, suggesting the effect of position varied across consecutive tilts. No prior study has characterized the cerebral oxygen saturation response to a 90° tilt in healthy term neonates.

A pilot study: Comparing a novel noninvasive measure of cerebrovascular stability index with an invasive measure of cerebral autoregulation in neonates with congenital heart disease.

Infants with congenital heart disease (CHD) may have impaired cerebral autoregulation (CA) associated with cerebral fractional tissue oxygen extraction (FTOE). We conducted a pilot study in nine CHD neonates to validate a noninvasive CA measure, cerebrovascular stability index (CSI), by eliciting responses to postural tilts. We compared CSI to an invasive measure of CA and to FTOE collected during tilts (FTOESpot). FTOESpot correlated with CSI, as did the change in FTOE during tilts, but CSI's correlation with impaired CA did not reach significance. Larger trials are indicated to validate CSI, allowing for noninvasive CA measurements and measurements in outpatient settings.

Ventilatory and Orthostatic Challenges Reveal Biomarkers for Neurocognition in Children and Young Adults With Congenital Central Hypoventilation Syndrome.

BACKGROUND: Children and young adults with congenital central hypoventilation syndrome (CCHS) are at risk of cognitive deficits. They experience autonomic dysfunction and chemoreceptor insensitivity measured during ventilatory and orthostatic challenges, but relationships between these features are undefined. RESEARCH QUESTION: Can a biomarker be identified from physiologic responses to ventilatory and orthostatic challenges that is related to neurocognitive outcomes in CCHS? STUDY DESIGN AND METHODS: This retrospective study included 25 children and young adults with CCHS tested over an inpatient stay. Relationships between physiologic measurements during hypercarbic and hypoxic ventilatory challenges, hypoxic ventilatory challenges, and orthostatic challenges and neurocognitive outcomes (by Wechsler intelligence indexes) were examined. Independent variable inclusion was determined by significant associations in Pearson's analyses. Multivariate linear regressions were used to assess relationships between measured physiologic responses to challenges and neurocognitive scores. RESULTS: Significant relationships were identified between areas of fluid intelligence and measures of oxygen saturation (SpO2) and heart rate (HR) during challenges. Specifically, perceptual reasoning was related to HR (adjusted regression [ß] coefficient, -0.68; 95% CI, 1.24 to -0.12; P = .02) during orthostasis. Working memory was related to change in HR (ß, -1.33; 95% CI, -2.61 to -0.05; P = .042) during the hypoxic ventilatory challenge. Processing speed was related to HR (ß, -1.19; 95% CI, -1.93 to -0.46; P = .003) during orthostasis, to baseline SpO2 (hypercarbic and hypoxic ß, 8.57 [95% CI, 1.63-15.51]; hypoxic ß, 8.37 [95% CI, 3.65-13.11]; P = .002 for both) during the ventilatory challenges, and to intrachallenge SpO2 (ß, 5.89; 95% CI, 0.71-11.07; P = .028) during the hypoxic ventilatory challenge. INTERPRETATION: In children and young adults with CCHS, SpO2 and HR-or change in HR-at rest and as a response to hypoxia and orthostasis are related to cognitive outcomes in domains of known risk, particularly fluid reasoning. These findings can guide additional research on the usefulness of these as biomarkers in understanding the impact of daily physical stressors on neurodevelopment in this high-risk group.

Factor Analysis of the Einstein Neonatal Neurobehavioral Assessment Scale in Infants with Congenital Heart Disease and Healthy Controls.

Background: Administration of the Einstein Neonatal Neurobehavioral Assessment Scale (ENNAS) can be time-consuming, and items can be highly correlated. We aimed to determine: (1) its factor analytic structure; (2) the validity of the factor structure; and (3) the associations of physiologic measures with factor scores. Methods: A factor analysis reduced 21 ENNAS items into 5 factors in 57 congenital heart disease (CHD) and 35 healthy infants. Multiple linear regressions examined the association of factor scores with group, gestational age, and physiologic variables. Results: 5-factor solution: 1 (Orienting Reflex), 2 (Extensor Axial Tone), 3 (Primitive Reflexes), 4 (Flexor Tone), 5 (Reflexive Tone Around Extremity Joints). Moderate to strong evidence supported: face, discriminant, and construct validity of these factors, with Factor 2 having the strongest. Conclusions: Components of Factor 2 may provide similar information about neonatal development, thus reducing the time for and burden of administration for researchers and clinicians.

Cerebral Autoregulation during Orthostatic Challenge in Congenital Central Hypoventilation Syndrome.

Rationale: Congenital central hypoventilation syndrome (CCHS) is a rare autonomic disorder with altered regulation of breathing, heart rate (HR), and blood pressure (BP). Aberrant cerebral oxygenation in response to hypercapnia/hypoxia in CCHS raises the concern that altered cerebral autoregulation may contribute to CCHS-related, variably impaired neurodevelopment. Objectives: To evaluate cerebral autoregulation in response to orthostatic challenge in CCHS cases versus controls. Methods: CCHS and age- and sex-matched control subjects were studied with head-up tilt (HUT) testing to induce orthostatic stress. Fifty CCHS and 100 control HUT recordings were included. HR, BP, and cerebral oxygen saturation (regional oxygen saturation) were continuously monitored. The cerebral oximetry index (COx), a real-time measure of cerebral autoregulation based on these measures, was calculated. Measurements and Main Results: HUT resulted in a greater mean BP decrease from baseline in CCHS versus controls (11% vs. 6%; P < 0.05) and a diminished increase in HR in CCHS versus controls (11% vs. 18%; P < 0.01) in the 5 minutes after tilt-up. Despite a similar COx at baseline, orthostatic provocation within 5 minutes of tilt-up caused a 50% greater increase in COx (P < 0.01) and a 29% increase in minutes of impaired autoregulation (P < 0.02) in CCHS versus controls (4.0 vs. 3.1 min). Conclusions: Cerebral autoregulatory mechanisms appear to be intact in CCHS, but the greater hypotension observed in CCHS consequent to orthostatic provocation is associated with greater values of COx/impaired autoregulation when BP is below the lower limits of autoregulation. Effects of repeated orthostatic challenges in everyday living in CCHS necessitate further study to determine their influence on neurodevelopmental disease burden.

Perspective on Cerebral Autoregulation Monitoring in Neonatal Cardiac Surgery Requiring Cardiopulmonary Bypass.

The autoregulation of cerebral blood flow protects against brain injury from transient fluctuations in arterial blood pressure. Impaired autoregulation may contribute to hypoperfusion injury in neonates and infants. Monitoring cerebral autoregulation in neonatal cardiac surgery as a guide for arterial blood pressure management may reduce neurodevelopmental morbidity. Cerebral autoregulation monitoring has been validated in animal models and in an adult trial autoregulation monitoring during bypass improved postoperative delirium scores. The nuances of pediatric cardiac disease and congenital heart surgery make simply applying adult trial findings to this unique population inappropriate. Therefore, dedicated pediatric clinical trials of cerebral autoregulation monitoring are indicated.

Cerebral oxygen saturation and cerebrovascular instability in newborn infants with congenital heart disease compared to healthy controls.

OBJECTIVE: Infants with Congenital Heart Disease (CHD) are at risk for developmental delays, though the mechanisms of brain injury that impair development are unknown. Potential causes could include cerebral hypoxia and cerebrovascular instability. We hypothesized that we would detect significantly reduced cerebral oxygen saturation and greater cerebrovascular instability in CHD infants compared to the healthy controls. METHODS: We performed a secondary analysis on a sample of 43 term infants (28 CHD, 15 healthy controls) that assessed prospectively in temporal cross-section before or at 12 days of age. CHD infants were assessed prior to open-heart surgery. Cerebral oxygen saturation levels were estimated using Near-Infrared Spectroscopy, and cerebrovascular stability was assessed with the response of cerebral oxygen saturation after a postural change (supine to sitting). RESULTS: Cerebral oxygen saturation was 9 points lower in CHD than control infants in both postures (ß = -9.3; 95%CI = -17.68, -1.00; p = 0.028), even after controlling for differences in peripheral oxygen saturation. Cerebrovascular stability was significantly impaired in CHD compared to healthy infants (ß = -2.4; 95%CI = -4.12, -.61; p = 0.008), and in CHD infants with single ventricle compared with biventricular defects (ß = -1.5; 95%CI = -2.95, -0.05; p = 0.04). CONCLUSION: CHD infants had cerebral hypoxia and decreased cerebral oxygen saturation values following a postural change, suggesting cerebrovascular instability. Future longitudinal studies should assess the associations of cerebral hypoxia and cerebrovascular instability with long-term neurodevelopmental outcomes in CHD infants.

Creatinine filtration kinetics in critically Ill neonates.

BACKGROUND: Creatinine values are unreliable within the first weeks of life; however, creatinine is used most commonly to assess kidney function. Controversy remains surrounding the time required for neonates to clear maternal creatinine. METHODS: Eligible infants had multiple creatinine lab values and were admitted to the neonatal intensive care unit (NICU). A mathematical model was fit to the lab data to estimate the filtration onset delay, creatinine filtration half-life, and steady-state creatinine concentration for each subject. Infants were grouped by gestational age (GA) [(1) 22-27, (2) >27-32, (3) >32-37, and (4) >37-42 weeks]. RESULTS: A total of 4808 neonates with a mean GA of 34.4 ± 5 weeks and birth weight of 2.34 ± 1.1 kg were enrolled. Median (95% confidence interval) filtration onset delay for Group 1 was 4.3 (3.71, 4.89) days and was significantly different than all other groups (p < 0.001). Creatinine filtration half-life of Groups 1, 2, and 3 were significantly different from each other (p < 0.001). There was no difference in steady-state creatinine concentration among the groups. CONCLUSIONS: We quantified the observed kidney behavior in a large NICU population as a function of day of life and GA using creatinine lab results. These results can be used to interpret individual creatinine labs for infants to detect those most at risk for acute kidney injury. IMPACT: One of the largest cohorts of premature infants to describe the evolution of kidney development and function over their entire hospitalization. New concept introduced of the kidney filtration onset delay, the time needed for the kidney to begin clearance of creatinine, and that it can be used as an early indicator of kidney function. The smallest premature infants from 22 to 27 weeks gestation took the longest time to begin and complete maternal creatinine clearance. Clinicians can easily compare the creatinine level of their patient to the normative curves to improve understanding of kidney function at the bedside.

Continuous cerebral hemodynamic measurement during deep hypothermic circulatory arrest.

While survival of children with complex congenital heart defects has improved in recent years, roughly half suffer neurological deficits suspected to be related to cerebral ischemia. Here we report the first demonstration of optical diffuse correlation spectroscopy (DCS) for continuous and non-invasive monitoring of cerebral microvascular blood flow during complex human neonatal or cardiac surgery. Comparison between DCS and Doppler ultrasound flow measurements during deep hypothermia, circulatory arrest, and rewarming were in good agreement. Looking forward, DCS instrumentation, alone and with NIRS, could provide access to flow and metabolic biomarkers needed by clinicians to adjust neuroprotective therapy during surgery.

Acute hypercarbia increases the lower limit of cerebral blood flow autoregulation in a porcine model.

OBJECTIVES: In the present study, our objective was to determine if hypercarbia would alter cerebral blood flow (CBF) autoregulation and reduce the ability of cerebrovascular reactivity monitoring to identify the lower limit of cerebrovascular autoregulation (LLA). METHODS: Anaesthetised juvenile pigs were assigned between two groups: normocarbia (control group, n = 10) or hypercarbia [high carbon dioxide (CO2) group, n = 8]. Normocarbia subjects were maintained with an arterial CO2 of 40 Torr, while the hypercarbia subjects had an increase of inspired CO2 to achieve an arterial pCO2 of >80 Torr. Gradual hypotension was induced by continuous haemorrhage from a catheter in the femoral vein, and the LLA was determined by monitoring cortical laser Doppler flux (LDF). Vascular reactivity monitoring was performed using the pressure reactivity index (PRx) and haemoglobin volume index (HVx). RESULTS: There were no sustained differences in ICP between groups. Autoregulation was present in both groups, despite elevation in pCO2.The control group had an average LLA of 45 mmHg (95% CI: 43-47 mmHg) and the high CO2 group had a LLA of 75 mmHg (95% CI: 73-77 mmHg). The detected LLA for each subject correlated with the level of pCO2 (spearman R = 0.8243, P < 0.0001). Both the PRx and HVx accurately detected the LLA despite the presence of hypercarbia. DISCUSSION: Hypercarbia without acidosis increases the observed LLA independent of alterations in ICP. Elevations in CO2 can impair cerebrovascular autoregulation, but if there is a sufficient increase in blood pressure above the CO2 altered LLA, then autoregulation persists.

Optic nerve sheath diameter measurement techniques: examination using a novel ex-vivo porcine model.

BACKGROUND: Ultrasound (U/S) and MRI measurements of the optic nerve sheath diameter (ONSD) have been proposed as intracranial pressure measurement surrogates, but these methods have not been fully evaluated or standardized. The purpose of this study was to develop an ex-vivo model for evaluating ONSD measurement techniques by comparing U/S and MRI measurements to physical measurements. METHODS: The left eye of post mortem juvenile pigs (N = 3) was excised and the subdural space of the optic nerve cannulated. Caliper measurements and U/S imaging measurements of the ONSD were acquired at baseline and following 1 cc saline infusion into the sheath. The samples were then embedded in 0.5% agarose and imaged in a 7 Tesla (7T) MRI. The ONSD was subsequently measured with digital calipers at locations and directions matching the U/S and direct measurements. RESULTS: Both MRI and sonographic measurements were in agreement with direct measurements. U/S data, especially axial images, exhibited a positive bias and more variance (bias: 1.318, 95% limit of agreement: 8.609) compared to MRI (bias: 0.3156, 95% limit of agreement: 2.773). In addition, U/S images were much more dependent on probe placement, distance between probe and target, and imaging plane. CONCLUSIONS: This model appears to be a valid test-bed for continued scrutiny of ONSD measurement techniques. In this model, 7T MRI was accurate and potentially useful for in-vivo measurements where direct measurements are not available. Current limitations with ultrasound imaging for ONSD measurement associated with image acquisition technique and equipment necessitate further standardization to improve its clinical utility.

Intracranial pressure and optic nerve sheath diameter as cephalic venous pressure increases in swine.

BACKGROUND: Nontraumatic, nonhydrocephalic increases in intracranial pressure (ICP) are often difficult to diagnose and may underlie spaceflight-related visual changes. This study looked at the utility of a porcine animal model of increasing cephalic venous pressure to mimic acute changes in ICP and optic nerve sheath diameter (ONSD) from cephalic venous fluid shifts observed during spaceflight. METHODS: Anesthetized juvenile piglets were assigned to groups of either naïve (N = 10) or elevated superior vena cava pressure (SVCP; N = 20). To elevate SVCP, a 6F custom latex balloon catheter was inserted and inflated to achieve SVCP of 20 and 40 mmHg for 1 h at each pressure. In both groups, serial measurements of ICP, internal jugular pressure (IJP), and external jugular pressure (EJP) were made hourly for 3 h, and ONSD of the right eye was measured hourly by ultrasound (US). RESULTS: There was a significant linear correlation between IJP and ICP (slope: 0.9614 +/- 0.0038, r = 0.9683). With increasing SVCP, resulting ONSD was also well correlated with the ICP (slope: 0.0958 +/- 0.0061, r = 0.7841). The receiver operating characteristic curve for ONSD in diagnosing elevated ICP had an area under the curve of 0.9632 with a sensitivity and specificity of 92% and 91%, respectively, for a cutoff of 5.45 mm. CONCLUSIONS: Increases in SVCP result in ICP changes that are well correlated with alteration in ONSD. These changes are consistent with observed ONSD changes monitored during spaceflight.

Magnitude of arterial carbon dioxide change at initiation of extracorporeal membrane oxygenation support is associated with survival.

Many patient factors have been associated with mortality from extracorporeal membrane oxygenation (ECMO) therapy. Pre-ECMO patient pH and arterial carbon dioxide (paCO2) have been associated with poor outcome and can be significantly altered by ECMO initiation. We hypothesized that the magnitude of change in paCO2 and pH with ECMO initiation could be associated with survival. We designed a retrospective observational study from a single tertiary care center and included all pediatric patients (age younger than 18 years) undergoing ECMO between 2002 and 2010. Electronic records were queried for demographics and clinical characteristics, including the arterial blood gas (ABG) pre- and post-ECMO initiation. Bivariate analysis compared ECMO course characteristics by outcome (survivor vs. nonsurvivor). Multivariable logistic regression was performed on factors associated with the outcome in the bivariate analysis at the significance level of p < .1. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were reported. We identified 201 patients with a median age of 10 days (range, 1 day to 16 years). Indications for ECMO were: respiratory failure (51%), cardiac failure (23%), extracorporeal cardiopulmonary resuscitation (21%), and sepsis (5%). Mortality, defined by death before discharge, was 37% (74 of 201). ABG data pre- and post-ECMO initiations were available in 84% (169 of 201). Age, pH, paCO2, indication, and intracranial hemorrhage were significantly associated with mortality (p < .05). After adjusting for potential confounders (age, use of epinephrine, volume of fluid administered, year of ECMO, ECMO indication, and duration of ECMO) by multivariable logistic regression, the magnitude of paCO2 change (> or =25 mmHg) was associated with mortality (adjusted OR, 2.21; 95% CI, 1.06-4.63; p = .036). The decrease in paCO2 with ECMO initiation was associated with mortality. Although this change in paCO2 is multifactorial, it represents a modifiable element of clinical management involving pre-ECMO ventilation, ECMO circuit priming, CO2 administration/removal, and may represent a future therapeutic target that could improve survival in pediatric ECMO.

Continuous cerebrovascular reactivity monitoring and autoregulation monitoring identify similar lower limits of autoregulation in patients undergoing cardiopulmonary bypass.

OBJECTIVES: Cerebrovascular autoregulation can be monitored with a moving linear correlation of blood pressure to cerebral blood flow velocity (mean velocity index, Mx) during cardiopulmonary bypass (CPB). Vascular reactivity can be monitored with a moving linear correlation of blood pressure to cerebral blood volume trended with near-infrared spectroscopy (hemoglobin volume index, HVx). We hypothesized that the lower limits of autoregulation (LLA) and the optimal blood pressure (ABPopt) associated with the most active autoregulation could be determined by HVx in patients undergoing CPB. METHODS: Adult patients (n = 109) who underwent CPB for cardiac surgery had monitoring of both autoregulation (Mx) and vascular reactivity (HVx). Individual curves of Mx and HVx were constructed by placing each in 5 mmHg bins. The LLA and ABPopt for each subject were then identified by both methods and compared for agreement by correlation analysis and Bland-Altman. RESULTS: The average LLA defined by Mx compared to HVx were comparable (66±13 and 66±12 mmHg). Correlation between the LLA defined by Mx and HVx was significant (Pearson r = 0.2867; P = 0.0068). The average ABPopt with the most robust autoregulation by Mx was comparable to HVx (75±11 and 74±13 mmHg) with significant correlation (Pearson r = 0.5915; P < or =0.0001). DISCUSSION: Autoregulation and vascular reactivity monitoring are expected to be distinct, as flow and volume have different phasic relationships to pressure when cerebrovascular autoregulation is active. However, the two metrics have good agreement when identifying the LLA and optimal blood pressure in patients during CPB.

The limitations of near-infrared spectroscopy to assess cerebrovascular reactivity: the role of slow frequency oscillations.

BACKGROUND: A total hemoglobin reactivity index (THx) derived from near-infrared spectroscopy (NIRS) has recently been introduced to assess cerebrovascular reactivity noninvasively. Analogously to the pressure reactivity index (PRx), THx is calculated as correlation coefficient with arterial blood pressure (ABP). However, the reliability of THx in the injured brain is uncertain. Although slow oscillations have been described in NIRS signals, their significance for assessment of autoregulation remains unclear. In the current study, we investigated the role of slow oscillations of total hemoglobin for NIRS-based cerebrovascular reactivity monitoring. METHODS: This study was based on a retrospective analysis of data that were consecutively recorded for a different project published previously. Thirty-seven patients with traumatic brain injury and admitted to Addenbrooke's Neurosciences Critical Care Unit between June 2008 and June 2009 were included. After artifact removal, we performed spectral analysis of the tissue hemoglobin index (THI, a measure of oxy- and deoxygenated hemoglobin) and intracranial pressure (ICP) signal. PRx and THx were calculated as moving correlations between ICP and ABP, and THI and ABP, respectively. The agreement between PRx and THx as a function of normalized power of slow oscillations (0.015-0.055 Hz) contained in the input signals was assessed performing between-subject and within-subject correlation analyses. Furthermore, the correlation between the THx values derived from the right and left sides was analyzed. RESULTS: The agreement between PRx and THx depended on the power of slow oscillations in the input signals. Between-subject comparisons revealed a significant correlation between THx and PRx (r = 0.80, 95% confidence interval 0.53-0.92, P < 0.01) for patients with normalized slow wave activity >0.4 in the THI signal, compared with r = 0.07 (95% confidence interval -0.40 to 0.51, P = 0.79) in the remaining files. Furthermore, within-subject comparisons suggested that THx may be used as a substitute for PRx only when there is an at least moderate agreement (r = 0.36) between the THx values derived from the right and left sides. CONCLUSIONS: Our results suggest that the NIRS-based cerebrovascular reactivity index THx can be used as a noninvasive substitute for PRx, but only during phases with sufficient slow wave power in the input signal. Furthermore, a good agreement between the THx measures on both sides seems to be a prerequisite for comparison of a global (PRx) versus the more local (THx) index. Nevertheless, noninvasive assessment of cerebrovascular reactivity may be desirable in patients without ICP monitoring and help to guide ABP management in these patients.

Thrombotic disease in critically ill children.

OBJECTIVES: To summarize a) epidemiology of arterial and venous thromboembolism, pulmonary embolism, and deep venous thrombosis in children; b) the risk factors for thrombosis in the pediatric intensive care unit; c) diagnostic techniques for arterial/venous thromboembolism; and d) the current recommendations for management and prevention of thromboembolic disease in critically ill children. DATA SOURCE: Literature review, using National Library of Medicine PubMed and the following terms: arterial, venous thromboembolism; deep venous thrombosis; pulmonary embolism; thrombosis; as well as citations of interest from these articles. STUDY SELECTION: Both pediatric and adult literature addressing thrombotic disease were reviewed. DATA EXTRACTION AND SYNTHESIS: Articles were chosen for more extensive discussion when containing prospective studies, guidelines for practice, or data in critically ill patients. When data in children were unavailable, applicable data in adults were referenced. Due to the paucity of data in critically ill children, available adult and pediatric data were combined with institutional experience to provide suggestions for current practice and future inquiry. CONCLUSIONS: Increasing awareness regarding the recognition and current approaches to management and prevention of thromboembolic disease in children is needed among pediatric intensivists, so outcome of these life-threatening processes might be improved.

Noninvasive monitoring of cerebrovascular reactivity with near infrared spectroscopy in head-injured patients.

Monitoring of cerebrovascular pressure reactivity (PRx) has diagnostic and prognostic value in head-injured patients, but requires invasive monitoring of intracranial pressure (ICP). Near infrared spectroscopy (NIRS) is a noninvasive method that is suitable for continuous detection of cerebral blood volume changes. We compared a NIRS-based index of cerebrovascular reactivity, called total hemoglobin reactivity (THx), against standard measurements of PRx in a prospective observational study. Forty patients with closed-head injury were monitored daily with arterial blood pressure (ABP), ICP, and a NIRS-based total hemoglobin index. PRx and THx were calculated as the moving correlation coefficients using 5-min time windows between 10-sec averaged values of ICP and ABP, and total hemoglobin index and ABP, respectively. A total of 120 recordings were performed between the median first (IQR 0.75-2) and fourth (IQR 2-6) day after head injury, giving a total duration of 1760 hours. PRx and THx demonstrated a significant association across averaged individual recordings (r = 0.49, p < 0.0001), and across patients (r = 0.56, p = 0.0002). Assessment of optimal cerebral perfusion pressure (CPP) and ABP using THx was possible in about 50% of recordings, and showed a significant agreement with the optimal CPP and ABP assessed with PRx. THx may be of diagnostic value to optimize therapy oriented toward restoration and continuity of cerebrovascular reactivity, especially in patients for whom direct ICP monitoring is not feasible.